Cytological diagnosis of sarcoidosis revisited: A state of the art review

TIMELY REVIEWSection Editor: Zubair Baloch, M.D., Ph.D.

Cytological Diagnosis ofSarcoidosis Revisited:A State of the Art ReviewRavi Mehrotra, M.D., M.I.A.C.* and Vishal Dhingra, M.D.

Diagnosis of sarcoidosis has never been an easy task. This isprimarily because there is no single diagnostic test that canclinch the diagnosis. Demonstration of granulomas remains anessential criteria, but as granulomatous inflammation can beseen in host of conditions, it is necessary to exclude all possiblecauses, as well as to correlate with other findings, before arriv-ing at the diagnosis of sarcoidosis. Cytology has been usedeffectively since the last few decades in demonstration ofgranulomas in various organs. Recent developments in variousfields of cytodiagnosis of sarcoidosis including transesopha-geal ultrasound-guided fine-needle aspiration and endobron-chial ultrasonograpy-guided transbronchial needle aspirationhave revolutionized this field. These techniques are safe, mini-mally invasive, and give real-time information during aspira-tion. In comparision to the conventional methods, these alloweasier sampling and have better sensitivity. In addition tothese methods, a variety of ancillary techniques are also uti-lized and are reviewed here. Diagn. Cytopathol. 2011;39:541–548. ' 2010 Wiley-Liss, Inc.

Key Words: sarcoidosis; cytological diagnosis; transesophagealultrasound-guided fine-needle aspiration; transbronchial fine nee-dle aspiration

Sarcoidosis is a chronic, multisystem, granulomatous dis-

order, of unknown etiology, primarily affecting the lung

and lymphatic systems of the body.1 This disease is char-

acterized by the formation of noncaseating epitheliod cell

granulomas, usually accompanied by multinucleated giant

cells, as a result of disordered immune regulation in ge-

netically predisposed individuals exposed to certain envi-

ronmental agents. The initial clinical presentation of sar-

coidosis is variable, depending on the organ systems

involved. The diagnosis is established when clinicoradio-

logic findings are supported by cytological or histological

evidence of noncaseating epitheliod cell granulomas

and other causes of granulomas have been, definitively,

excluded.2

History

A common saying with regards to sarcoidosis is: ‘‘Moreis unknown about sarcoidosis than is known.’’

In 1877, Dr. Jonathan Hutchinson, a London surgeon-

dermatologist, first described the findings of a 50-year-old

man who had large purple skin plaques on the hands and

feet and similar skin lesions in a 64-year-old woman, on

her face and arms. The disease was then known as Hutch-

inson’s disease.

However, in 1889, Dr. Cesar Boeck, a Norwegian der-

matologist coined today’s name for the disease from the

Greek words ‘‘sark’’ and ‘‘oid,’’ meaning flesh-like,

named the process ‘‘multiple benign sarcoid of the skin.’’

He also showed that many patients also had sarcoid

lesions in the lymph nodes and lungs.

Dr. S. B. Wolbach, in 1911, described Asteroid bodies,

inclusion seen in sarcoid granulomas, in his article enti-

tled ‘‘A New Type of Cell Inclusion, not Parasitic, Asso-

ciated with Disseminated Granulomatous Lesions’’ as

star-shaped structures found within the cytoplasm of mul-

tinucleated giant cells.3

In 1958, scientists from all over the world met at the

Brompton Hospital in London for a conference about sar-

coidosis. Since then there has been a yearly international

sarcoidosis conference and a scientific journal for sarcoid-

osis. The history of sarcoidosis has been comprehensively

reviewed by Sharma.4

This article was presented, in part, at the ‘‘International conference onpathology of chest disorders: an integrated approach’’ organized by Pul-monary Pathology Society division of United States and Canadian Acad-emy of Pathology and Pulmonary Pathology Society of India at V.P.Patel Chest Institute, University of Delhi in Dec. 2008.

Division of Cytopathology, Department of Pathology, Moti Lal NehruMedical College, Allahabad, India

*Correspondence to: Ravi Mehrotra, M.D., M.I.A.C., Professor ofPathology, Moti Lal Nehru Medical College, 16/2, Lowther Road,Allahabad 211002, India. E-mail: [email protected]

Received 20 April 2010; Accepted 1 May 2010DOI 10.1002/dc.21455Published online 14 October 2010 in Wiley Online Library

(wileyonlinelibrary.com).

' 2010 WILEY-LISS, INC. Diagnostic Cytopathology, Vol 39, No 7 541

Epidemiology

Sarcoidosis occurs throughout the world but its incidence

varies widely in different countries and ethnic groups.

The disease is more prevalent in certain groups, such as

African Americans and Northern Europeans. The recorded

prevalence is *10 and 40/100,000 populations in the US

and Europe, respectively.5 In the United States, rates are

highest in the Southeast; it is *10 times higher in Ameri-

can blacks than in whites. On the other hand, the disease

is uncommon in Chinese and Southeast Asians.

The prevalence of sarcoidosis is higher in women than

in men with an average incidence of 16.5/100,000 in men

and 19/100,000 in women. Sarcoidosis is rare before

adulthood and in the elderly. The disease usually presents

before 40 years of age, peaking in those aged 20–29.

There is a second smaller peak in women over age 50.6

Diagnosis

To establish a diagnosis of sarcoidosis it is necessary that

granulomata must be present in two or more organs—

with no agent known to cause a granulomatous response

being identified.7 A diligent search should be made for

other causes of granulomatous inflammation, including

mycobacteria, fungi, parasites, and foreign bodies.

Although sarcoid granulomas have no specific diagnos-

tic features, there are, however, certain characteristics that

point toward the diagnosis. A diagnostic algorithm that

would be helpful to arrive at cytological diagnosis of sar-

coidosis is proposed (Fig. 1). The sarcoid granuloma con-

sists of a compact (organized) collection of mononuclear

phagocytes (macrophages or epitheliod cells) typically

without necrosis (Figs. 2A, B and 3A–C).8 Usually giant

cells are found within the sarcoid granulomas and these are

usually surrounded by a peripheral mantle of lymphocytes.

A variety of inclusions may be present, such as Schau-

mann’s bodies, asteroid bodies (Figs. 2C, D and 3D), bire-

fringent crystals, and Hamazaki-Wesenberg bodies; how-

ever, these inclusions are nonspecific and not diagnostic of

sarcoidosis.9

Since sarcoidosis is known to resolve spontaneously in

more than 70% of patients, the need for cytological/tissue

diagnosis has been the subject of hot debate. The argu-

ments of the opponents of cytological/tissue diagnosis are

based on risk/benefit and cost/benefit considerations,

while those of its proponents are based on the individual

patient’s perspective.10

Cytology

Cytology can be of immense value in the diagnosis of

sarcoidosis. Cytological evaluation can be easily done in

patients with lung and lymph node involvement. As these

organs are involved in majority of the patients with sar-

coidosis and morphological evidence of granulomas is

essential for diagnosis, cytology has an unequivocal role

in diagnostic work up in patient of sarcoidosis. The im-

portant role of fine needle aspiration cytology (FNAC) in

diagnosis and its underutilization was highlighted by

Tambouret et al.11 FNAC when used in conjunction with

clinical findings, radiological and laboratory investiga-

tions, is a useful tool in the diagnosis of sarcoidosis. The

procedure is a simple, safe, cost-effective and can be eas-

ily performed in any out-patient setting, with turnaround

time much less than that of conventional histopathology.

However, in spite of these advantages, cytology is rou-

tinely utilized only in few centers to arrive at a diagnosis

of sarcoidosis.

Cytology is used primarily to demonstrate granulo-

mas(s) in various organs that are affected by sarcoidosis.

It is preferred to demonstrate granuloma in at least two

organs and it is important to exclude other causes of gran-

ulomatous inflammation. Therefore, a portion of the speci-

men should be submitted for fungal and mycobacterial

cultures. Smojver-Jezek et al. studied 116 patients with

mediastinal/hilar lymphadenopathy and 171 transbronchial

fine needle aspirations (TBFNA) were performed from

different lymph nodes.12 Adequate lymph node samples

were obtained in 157 of 171 (91.8%) TBFNA while 14 of

171 (8.2%) samples were inadequate. Cytological findings

consistent with sarcoidosis were present in 133 of 157

(84.7%) samples and in 79 of 88 (89.8%) of patients.

Multinucleated Langhan’s giant cells with epithelioid cells

Fig. 1. Proposed algorithm for the diagnosis of sarcoidosis.

MEHROTRA AND DHINGRA

542 Diagnostic Cytopathology, Vol 39, No 7

Diagnostic Cytopathology DOI 10.1002/dc

and variable numbers of lymphocytes, with or without

minimal necrosis, as the elements of granuloma were

found in 104/157 (66.2%) of TBFNA samples and in 63/

88 (71.6%) of patients. Small groups or scattered epithe-

lioid cells with lymphocytes, without multinucleated giant

cells or necrosis were considered as findings consistent

with sarcoidosis in 29/157 (18.5%) of TBFNA samples

and 16/88 (18.2%) patients. In 63.6% of patients, TBFNA

cytology was the only morphological evidence of granu-

lomatous inflammatory disease.

Lungs and Hilar Lymph Nodes

Lungs are, by far, the most common organ involved, and

the chest radiograph is abnormal in over 95% of patients

with sarcoidosis.13 The most common abnormalities

encountered are lymph node enlargement and parenchy-

mal lung involvement with fine or coarse reticulations.14

The most characteristic finding is symmetrical bilateral

hilar lymph node enlargement. In fact, sarcoidosis is the

most common cause of bihilar lymphadenopathy in the

Western world.15

Approximately 50% of patients with sarcoidosis have

impaired lung function tests with a restrictive pattern.

Sarcoidosis constitutes 2% of interstitial lung disease.16

Various modalities can used to confirm the presence of

granulomas in lung/hilar tissue.

Bronchoalveolar Lavage (BAL)

In patients with sarcoidosis, cytological findings in BAL

include normal or mildly elevated total cell predominance

of lymphocytes, usually normal percentage of eosinophils

and neutrophils, as well as an absence of plasma cells and

foamy alveolar macrophages.17 Bronchoalveolar lavage

(BAL) with examination of lymphocyte populations

(CD4/CD8 ratio) is sometimes used as a complementary

Fig. 2. (A) Cytology smear showing cluster of epithelioid cell along with lymphocytes, forming granulomas (MGG, 3400). (B) Higher power showingepithelioid cells granuloma (MGG, 31000). (C) Smear showing an asteroid body within a giant cell (MGG, 31000). (D) Cell Block showing an aster-oid body (H&E, 3400). [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]

CYTOLOGICAL DIAGNOSIS OF SARCOIDOSIS

Diagnostic Cytopathology, Vol 39, No 7 543


test for the diagnosis of sarcoidosis. In one study, a lym-

phocyte CD4/CD8 ratio of greater than 3.5 had a sensitiv-

ity of 53%, specificity of 94%, a positive predictive value

of 76%, and a negative predictive value of 85% for the

diagnosis of sarcoidosis.18 Ozdemir et al. reported on 50

patients of sarcoidosis and showed that the BAL fluid

concentration of an apoptotic molecule, CD95 (Fas), was

significantly higher in patients with chronic sarcoidosis

compared with those with spontaneous remission.19

Another study by Heron et al. evaluated the utility of the

integrin CD103, expressed on CD4+ T lymphocytes in the

BAL fluid, in the diagnosis of sarcoidosis in 56 patients.

These authors have shown that the combined use of the

CD103+CD4+/CD4+ ratio (<0.2) with either the BAL

CD4+/CD8+ ratio (>3) or the relative BAL/peripheral

blood CD4+/CD8+ ratio (>2) could discriminate sarcoido-

sis from other interstitial lung diseases with a sensitivity

of 66% and a specificity of 89%.20

Transbronchial Fine Needle Aspiration (TBFNA)

In the 1950s Brouet and Euler introduced transbronchial

needle aspiration through a rigid bronchoscope.21 But it

was Wang et al., in 1978, who used transbronchial needle

aspiration with fibreoptic bronchoscopy, thereby avoiding

more invasive surgical procedures, such as mediastino-

scopy.22–24 The method was used for sampling of intralumi-

nal lesions. In the last two decades its primary indication

has been to obtain material from mediastinal and/or hilar

nodes in staging of lung carcinomas and differential diagno-

sis of reactive lymphadenopathy including sarcoidosis.25,26

Pisircriler et al. diagnosed intrathoracic sarcoidosis by

visualizing epithelioid cell granulomas in 441 patients,

based on cytologic examinations of transbronchial aspira-

tion specimens from mediastinal lymph nodes.27 The

results were confirmed histologically using transbronchial

lung biopsy (TBLB) or thoracoscopy. The sensitivity of

cytology was 92%. In another study, Tambouret et al. an-

Fig. 3. (A) Histopathology section showing epthelioid cell granulomas (H&E 340). (B) Higher power showing epithelioid cells granuloma (H&E.3100). (C) Histopathology section showing granulomas (H&E, 3400). (D) Histopathology section showing granulomas with asteroid body (arrow)(H&E, 31000). [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]




alyzed the use of FNAC in the clinical examination of 32

patients with noncaseating granulomas, detected in all and

proven by histology in half of the patients.11

Smojver-Jezek found the sensitivity of TBFNA cytology

in sarcoidosis presenting as mediastinal/hilar lymphadenopa-

thy to be 78.7% and specificity 92.3%. The positive predic-

tive value for sarcoidosis was 97.8% and negative predictive

value was 60%. Overall diagnostic accuracy of TBFNA

cytology in the diagnosis of mediastinal/hilar sarcoidosis

was 86.2%.12

The diagnostic yield of TBFNA in the diagnosis of

mediastinal/hilar sarcoidosis is dependent on the needle

gauge, the brochoscopist’s skill and the number of nodes

sampled. Whenever possible, sampling of more than one

nodal region is advised to increase diagnostic yield. Triso-

lini et al. showed cytologic TBFNA yielded more material

than that of histologic samples in both the patient-based

(79% versus 30%) and the procedure-based analyses

(70% versus 22.5%), a finding that contrasts with reports

from other investigators.26 Though diagnostic yields in

TBNA are similar to those of transbronchial lung biopsy

(TBLB),28 the major advantage is that there is lesser mor-

bidity and lower chances of potential complications like

pneumothorax and bleeding with TBLB.

Endoscopic Ultrasonograpy-GuidedFine-Needle Aspiration

Cytological diagnosis of sarcoidosis got a fillip with

development of linear echoendoscopes. It is now possible

to do transesophageal ultrasound-guided fine-needle aspira-

tion (EUS-FNA) and endobronchial ultrasonograpy-guided

transbronchial needle aspiration (EBUS-TBNA). These

methods are safe, minimally invasive, and give real-time

information for aspirations.29

The combination of EUS along with simultaneous

FNAC in mediastinal lymphadenopathy is well established

in diagnosis and staging of carcinoma lung,2–8 however,

cases of sarcoidosis using EUS-FNA and EBUS-TBNA

are relatively less well recognized. Mishra et al. recently

reported seven cases of sarcoidosis in 108 EUS-guided

mediastinal FNA procedures.30 Williams et al. diagnosed

sarcoidosis in five men by aspirating granulomatous mate-

rial from bulky posterior nodes. The patients represented

a subgroup from series of 120 patients undergoing EUS-

FNA of mediastinal lymph nodes.31 All of the patients

showed a clinical response to steroid treatment. Lohela et

al. diagnosed granulomatous inflammation using ultra-

sound-guided FNA cytology of lymph nodes.32 The

results were consistent with sarcoidosis in 88% of the

patients, and the diagnosis could be confirmed on histol-

ogy and clinical follow-up.

In a study conducted on 19 patients of suspected sar-

coidosis, using EUS-FNA with a linear echoendoscope

and a 22-gauge Hancke-Vilman needle, Fritscher et al.,

reported the overall diagnostic accuracy and sensitivity of

EUS-FNA in the diagnosis of sarcoidosis as 94 and

100%, respectively.33

Several studies have showed diagnostic yield of real-

time EBUS-TBNA to be 85–93%.34–36 Garwood et al.

demonstrated that the yield of EBUS-TBNA exceeded

80% at five passes, with no further increase in yield even

after seven passes.34

The usefulness of EBUS-TBNA in patients with suspi-

cion of sarcoidosis has been demonstrated by studies by

Wong et al. and Oki et al.35,36 EBUS-TBNA was diagnos-

tic in 85–91.8% of patients with a final diagnosis of sar-

coidosis. The negative predictive value (NPVs) found in

these studies were 11 and 12.5%, respectively. Advantage

of EBUS-TBNA over EUS-FNA is its greater ability to

access different hilar lymph nodes and nodes situated an-

terolateral to the trachea, which are more commonly

involved in sarcoidosis. Besides this, BAL and TBLB can

also be done along with bronchsocopy done for EBUS

TBNA.

In a recent study, von Bartheld et al., demonstrated that

cell-block analysis added to conventional cytological eval-

uation of EUS aspirates results in a high yield in detect-

ing granulomas in patients with suspected sarcoidosis and

reduces the false-negative rate substantially.37

Biopsy

Transbronchial lung biopsy (TBLB) is one of the pre-

ferred diagnostic methods for pulmonary sarcoidosis. Its

diagnostic accuracy is reported to be about 70% (range

40–90).38,39 It is recommended that four to five lung biop-

sies be performed to maximize the diagnostic yield.

TBLB is more likely to be diagnostic in patients with

parenchymal disease on chest radiograph (radiographic

stage II or III) than in those with a normal lung paren-

chyma (radiographic stage 0 or I).38

Endobronchial biopsy has a diagnostic yield of 40–60%

for sarcoidosis. Furthermore, endobronchial biopsy can be

performed with the TBLB procedure and has been shown

to increase the diagnostic yield for sarcoidosis above that

by using TBLB alone.40

Mediastinoscopy

Mediastinoscopy used to be the ‘‘gold standard’’ for mak-

ing the diagnosis of pulmonary sarcoidosis, but it is more

invasive and costly, as well as having a greater morbidity

than TBLB or TBNA. Therefore, mediastinoscopy should

be reserved for patients with negative TBNA findings.41,42

Head and Neck

In the head and neck region, salivary glands and lymph

nodes are often involved, in patients with sarcoidosis.

These sites can be easily accessed, for cytology, by con-

ventional FNAC, as they present with palpable mass(es).




Mondal et al., in 1993, diagnosed sarcoidosis in 18 cases

presenting with palpable lymphadenitis in the head and

neck region.43 Salivary gland enlargement, is well known

in sarcoidosis. Aggarwal et al. reported sarcoidosis in two

presenting with bilateral parotid gland enlargement and

one with bilateral submandibular gland enlargement, by

FNAC.44 Smears showed noncaseating epithelioid cell

granulomas with or without giant cells and salivary gland

acini with varying degrees of degenerative changes. After

excluding other granulomatous lesions, sarcoidosis was

suggested and was subsequently proved in all three cases.

Asteroid bodies have been reported, in both lymph node

and parotid smears, however these are uncommonly

found.45 The authors group have diagnosed four such

cases on FNAC of the head and neck region with the

diagnosis being supported by angiotensin-converting

enzyme levels and confirmation by histology (Unpub-

lished Observation). FNAC, therefore, may be considered

a useful diagnostic modality in cases of sarcoidosis pre-

senting primarily with head and neck involvement.

Ancillary Techniques

Elevated serum angiotensin-converting enzyme level, are

seen in 50–60% patients. Serum angiotensin-converting

enzyme (SACE) is produced in the epithelioid cell of the

sarcoid granuloma and its levels reflect the total granuloma

burden in sarcoidosis.46,47 Although an elevated SACE was

initially thought to be diagnostic of sarcoidosis it is neither

sensitive nor specific diagnostic marker of sarcoidosis and

does not reliably correlate with disease activity or its prog-

nosis.48 Elevated levels of lysozyme are also seen in the

two-thirds of patients of sarcoidosis.49 They are derived

from the macrophage and correlate with SACE levels.

Biochemical abnormalities that have been described in

patients of sarcoidosis are hypercalcaemia, hypercalciuria,

hyperuricaemia, elevated serum aminotransferase, alanine

aminotransferase, and alkaline phosphatase.

Pulmonary function tests in typically show restrictive

pattern with impaired findings in more than half of

patients of sarcoidosis. Diffusing capacity of the lung for

carbon monoxide (DLCO) and the vital capacity test are

sensitive parameters to assess the pulmonary function.

Bilateral hilar adenopathy on chest radiograph suggests

the diagnosis of sarcoidosis, especially if the patient has

no fever, night sweats, or weight loss.10,15 Findings on

chest high-resolution computed tomography (HRCT) may

be more specific for the diagnosis of sarcoidosis than the

chest radiograph, although inadequate for the diagnosis to

be made without histologic confirmation.50 Gallium-67

(67Ga) scans show characteristic uptake, Panda/lambda sign

in patients with sarcoid lesions are positive; however, it has

been observed that transferrin receptor rapidly downregu-

lates after few months of systemic corticosteroid therapy,

possibly leading to a false-negative gallium scan.51 The

18F-fluorodeoxyglucose (FDG)-PET can also be of value

for evaluating systemic inflammatory activity,52 and is more

sensitive than gallium scanning.53,54 More recently, Kaira et

al., demonstrated that combination of L-[3-18F]-a-methyl-

tyrosine (18F-FMT) with conventional FDG-PET is more

useful in discriminating sarcoidosis from malignancy.55

To demonstrate cardiac involvement of sarcoidosis

recent studies have shown cardiac MRI to be a useful

diagnostic tool. In 10 patients with clinically diagnosed

cardiac sarcoidosis, Tadamura et al. have demonstrated

that delayed enhancement in cardiac MRI is useful for the

early detection of cardiac involvement having a sensitivity

of 100%, and was more specific and sensitive than echo-

cardiography, thallium and gallium scintigraphy.56

Use of genetic testing, though seems to hold promise

for the future, is yet to achieve clinical relevance. In a

recent study by Grunewald and Eklund showed that, in

patients with Lofgren’s syndrome, *99% of the human

leukocyte antigen (HLA) DRB1_0301/DQB1_0201-posi-

tive patients showed a spontaneous remission, whereas

only 55% of the HLA-DRB1_0301/DQB1_0201-negative

patients had a spontaneous remission.57

Kveim-Stilzbachs test is a diagnostic test of historical

importance. Splenic suspension from a spleen involved

with sarcoidosis is inoculated intradermally.58 However,

as the sensitivity and specificity vary depending upon the

spleen that is used and the suspension is not approved

Food and Drug Administration, this test is not considered

as a standard diagnostic test for sarcoidosis and is rarely

performed nowadays.50

Pitfalls of Cytological Assessmentof Sarcoid Granulomas

Tuberculosis may also present as noncaseating granulo-

mas. As it is primarily a pulmonary disease, it may present

as a diagnostic dilemma, especially in those parts of the

world where it has high prevalence. To make this distinc-

tion a suspicious clinical history of tuberculosis (pyrexia,

night sweats, recent travel to endemic areas, no previous

BCG vaccination) coupled blood, sputum or urine tests for

AFB, culture, PCR, and good response to anti-tuberculous

drugs would therapy supports the diagnosis of tuberculo-

sis. This is depicted in a tabular form to help distinguish

between granulomas of these two diseases (Table I).

Another pitfall may be finding noncaseous granulomas

in sarcoid reaction. These are morphologically identical to

the granulomas of sarcoidosis. Sarcoid reactions have

been reported in patients with various lymphomas, non-

small cell carcinoma of the lung, germ call neoplasm ei-

ther in lymph nodes draining the malignancy or in remote

lymph node stations.59 Interestingly, in the lung and other

organs, sarcoidosis or sarcoid reaction may sometimes

resemble a malignancy. These sarcoid-like granulomas

appear to represent a local T cell-mediated immune




reaction,60 possibly due to the shedding of antigens or

other factors from the tumor tissue, but reportedly differ

from sarcoid granulomas since they additionally contain

B cells within the granulomas.61 The various confounding

factors have been recently reviewed by Cameron et al.62

Conclusion

As there is no single confirmatory diagnostic test for sar-

coidosis, its diagnosis has always remained a daunting

task for both physicians and pathologists. However, recent

developments in diagnostic modalities have gone a long

way to facilitate and ease this challenge. Newer techni-

ques to sample lesions, like EUS-FNA and EBUS-TBNA

for cytological analysis, hold lot of promise. These diag-

nostic procedures, being minimally invasive, are a lot

safer and have sensitivity comparable to the standard pro-

cedures such as TBLB and/or mediastinoscopy which are

routinely used to establish tissue diagnosis for sarcoidosis.

We therefore believe, in the light of data that has emerged

from various studies, that cytology aided by these novel

methods of aspirating material is an useful addition, if not

an alternative, in the diagnosis of this entity.

Acknowledgments

The authors gratefully acknowledge permission to use

Figs. 2C and D from Drs. Jorns/Knoepp from University of

Michigan, Ann Arbor, MI and Fig. 3D from Dr. Shyama

Jain of Maulana Azad Medical College, Delhi, India.

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Table I. Differences Between Granulomas of Tuberculosisand Sarcoidosis

Criteria Sarcoidosis Tuberculosis

Epithelioid cell granuloma +++ +++Caseating cell necrosis, presentsas ‘‘dirty background’’

+ ++

Langhans’ giant cells � +++Histiocytic-type giant cells + ++Granulocytes + +++ZN stain for AFB � +++

Modified from table by Fritscher-Ravens et al.33

+, sometimes positive; ++, often positive; +++, strongly positive;�, usually negative.




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Cytological diagnosis of sarcoidosis revisited: A state of the art review

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